Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan

Clinical Microbiology and Infection, Journal Year: 2021, Volume and Issue: 27(12), P. 1861.e1 - 1861.e5

Published: Aug. 8, 2021

Language: Английский

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Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients

American Journal of Transplantation, Journal Year: 2021, Volume and Issue: 22(2), P. 634 - 639

Published: Sept. 22, 2021

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response vaccination. We analyzed factors related vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against spike S1 subunit their neutralization capacity after were 225 KTRs compared 176 controls. After the vaccination, 56 (24.9%) became seropositive of whom 68% had neutralizing antibodies. This was significantly lower controls (239 [78-519] BAU/ml versus 1826 [560-3180] for controls, p < .0001). The strongest predictor mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF-free regimen highly associated with seroconversion (OR 13.25, 95% CI 3.22-54.6; .001). contrast, other immunosuppressive drugs no significant influence. 187 out treated MMF 26 (13.9%) developed 23 these daily dose ≤1 g. Furthermore, higher trough concentrations correlated antibody titers (R -0.354, .001) supporting dose-dependent unfavorable effect MMF. Our data indicate modification could lead improved response.

Language: Английский

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Paxlovid: Mechanism of Action, Synthesis, and In Silico Study

BioMed Research International, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: July 7, 2022

In this work, the discovery and description of PF-07321332, a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, excellent selection off-target vivo immune profiles are reported. Various drugs novel compound candidates for treatment COVID-19 pandemic have been developed. PF-07321332 (or nirmatrelvir) is new drug developed by Pfizer. response to pandemic, Pfizer has COVID vaccine 2022 will launch its anti-SARS-Cov-2 (PI). The combination ritonavir nirmatrelvir under study phase III clinical trial brand name Paxlovid. Paxlovid an active 3Cl inhibitor. exerts efficacy inhibiting necessary viral replication procedure. Proteases cleave several sites polyprotein where pyrrolidone was replaced flexible glutamine. Due there high demand synthesis development drug. Herein, we report synthetic route mechanism action recently published on nirmatrelvir. Also, comparison performance two antiviruses (molnupiravir described. This review be helpful different disciplines such as biochemistry, organic chemistry, medicinal pharmacology.

Language: Английский

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Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 114990 - 114990

Published: July 7, 2023

Language: Английский

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Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review

Critical Reviews in Clinical Laboratory Sciences, Journal Year: 2022, Volume and Issue: 59(6), P. 373 - 390

Published: Feb. 28, 2022

With the advent of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses SARS-CoV-2 infections. Despite effectiveness safety, inter-individual immune response heterogeneity has observed recipients mRNA-based vaccines. As a novel disease, specific mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral plays crucial role affording immunoprotection preventing debilitating sequelae from COVID-19. such, paper focused on possible effects age, sex, serostatus, comorbidities (i.e. total antibodies, IgG, and/or IgA) different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search literature was performed through PubMed, Cochrane CENTRAL, Google Scholar, Science Direct, medRxiv, Research Square. Studies were included if they reported 32 studies identified reviewed, percent differences means antibody levels calculated comparison. Findings revealed older individuals, male seronegativity, those with more mounted less response. Given these findings, recommendations proposed regarding current vaccination practices. These include giving additional immunocompromised elderly populations. Another recommendation conducting clinical trials combined scheme vaccines, protein vector-based

Language: Английский

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Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

npj Vaccines, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 28, 2022

Abstract Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following first second vaccine doses, again 3 months dose, 100 adult PLWH 152 controls. All were receiving suppressive antiretroviral therapy, median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm , though nadir ranged as low <10 . After adjustment for sociodemographic, health vaccine-related variables, infection was associated lower anti-RBD antibody concentrations activity after dose. Following two doses however, not significantly magnitude any humoral response multivariable adjustment. Rather, older age, a higher burden chronic conditions, dual ChAdOx1 vaccination doses. No significant correlation observed between recent or PLWH. These results indicate that well-controlled loads healthy range generally mount strong initial vaccination. Factors including co-morbidities, brand, durability rise new variants will influence when benefit from additional Further studies who are treatment have needed, longer-term assessments durability.

Language: Английский

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Comparison of SARS-CoV-2 anti-spike receptor binding domain IgG antibody responses after CoronaVac, BNT162b2, ChAdOx1 COVID-19 vaccines, and a single booster dose: a prospective, longitudinal population-based study

The Lancet Microbe, Journal Year: 2022, Volume and Issue: 3(4), P. e274 - e283

Published: Feb. 9, 2022

Vaccination is an efficient strategy to control the COVID-19 pandemic. In north Cyprus, vaccine distribution started with CoronaVac followed by BNT162b2, and ChAdOx1 vaccines. An option obtain a third booster dose BNT162b2 or was later offered people fully inoculated CoronaVac. There are few simultaneous comparative real-world antibody data for these three vaccines as well boosters after vaccination. Our study aimed at evaluating responses vaccination schemes.

Language: Английский

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Current Developments and Challenges of mRNA Vaccines

Annual Review of Biomedical Engineering, Journal Year: 2022, Volume and Issue: 24(1), P. 85 - 109

Published: March 1, 2022

mRNA vaccines have brought about a great revolution in the vaccine fields owing to their simplicity and adaptability antigen design, potential induce both humoral cell-mediated immune responses demonstrated high efficacy, rapid low-cost production by using same manufacturing platform for different vaccines. Multiple been investigated infectious diseases cancers, showing significant superiority other types of Although success has achieved control coronavirus disease 2019 pandemic, there are still multiple challenges future development In this review, most recent developments against cancers summarized an overview field. Moreover, also discussed on basis these developments.

Language: Английский

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Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial

The Lancet Respiratory Medicine, Journal Year: 2022, Volume and Issue: 10(9), P. 840 - 850

Published: June 27, 2022

BackgroundImmunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses S1 receptor-binding domain (S1-RBD) SARS-CoV-2 spike protein compared with uninterrupted in patients immune-mediated inflammatory diseases.MethodsWe did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial 26 hospitals UK. recruited adults from rheumatology and dermatology clinics who had been diagnosed disease (eg, rheumatoid arthritis, psoriasis or without axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, systemic lupus erythematosus) were taking low-dose weekly (≤25 mg per week) for at least 3 months. Participants also to have received two primary doses UK vaccination programme. randomly assigned participants (1:1), using centralised validated computer randomisation program, suspend 2 weeks their (suspend group) continue as usual (continue group). Participants, investigators, clinical research staff, data analysts unmasked, while researchers doing laboratory analyses masked group assignment. The outcome was S1-RBD titres 4 receiving dose, assessed intention-to-treat population. This is registered ISRCT, ISRCTN11442263; following pre-planned interim analysis, recruitment stopped early.FindingsBetween Sept 30, 2021 March 3, 2022, we 340 participants, whom 254 included analysis one groups: 127 group. Their mean age 59·1 years, 155 (61%) female, 130 (51%) 86 (34%) arthritis. After weeks, geometric titre 22 750 U/mL (95% CI 19 314–26 796) 10 798 (8970–12 997) group, ratio (GMR) 2·19 1·57–3·04; p<0·0001; mixed-effects model). increased response consistent across administration route, type disease, age, platform, history infection. There no intervention-related serious adverse events.InterpretationA people diseases resulted enhanced boosting vaccination. intervention simple, low-cost, easy implement, could potentially translate efficacy duration protection susceptible groups.FundingNational Institute Health Care Research.

Language: Английский

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Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(7), P. 1124 - 1137

Published: May 22, 2023

Abstract The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity older individuals. A functional GC requires co-ordination multiple cell types across time space, particular its two functionally distinct compartments: light dark zones. In aged mice, there is CXCR4-mediated mislocalization T follicular helper (T FH ) cells to zone a compressed network dendritic (FDCs) zone. Here we show that localization critical for antibody expansion FDC upon immunization. smaller mice were corrected by provision colocalize FDCs using CXCR5. This demonstrates age-dependent defects are reversible shows support stromal responses vaccines.

Language: Английский

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